| 
 R.
Frank Cook, PhD
Maxwell H. Gluck Equine Research Center
Department of Veterinary Science
University of Kentucky Lexington, Kentucky 40546-0099
At present much of my research is focused on Equine Infectious
Anemia Virus (EIAV) a lentivirus closely related to Human
Immunodeficiency Virus (HIV) that has the capability to infect
all members of the horse family. Although EIAV does not induce
chronic immunodeficiency, infection with some strains can
result in death while others may produce severe recurring
bouts of disease characterized by high fever, thrombocytopenia,
weight loss and anemia.
Lentiviruses have evolved numerous sophisticated strategies
to evade elimination by host immune responses and so infections
are for life. However in many cases the equine immune system
eventually “learns” to control viral replication
keeping the EIAV burden below the threshold levels required
to cause disease and creating a long-term inapparent carrier.
Much of my past research at the Gluck Center has involved
the production of chimeric infectious molecular clones to
identify genetic determinants of pathogenesis associated with
certain virulent EIAV strains. Furthermore we have produced
a different series of infectious molecular clones by site-directed
mutagenesis techniques to characterize amino acid residues
that confer generalized resistance to neutralizing antibodies.
This is a survival trait employed by EIAV and other lentiviruses
to ensure that neutralization only occurs in the presence
of very high concentrations of antibody.
My most recent research interests are in the field of vaccine
design. Vaccines are generally successful when they duplicate
natural fully protective immune responses induced by an infection.
Unfortunately, natural immune responses are only partially
protective against lentiviruses suggesting that to be completely
effective EIAV vaccines will need to stimulate responses that
exceed the normal repertoire. However such extraordinary responses
may be achievable by combining some of the powerful immunostimulatory
equine cytokines that have recently become available with
novel presentation of viral antigens made possible by the
inherent flexibility of genetic immunization techniques.
In addition to EIAV research I intend to capitalize on previous
experience in genetic engineering to develop viral and non-viral
gene delivery systems for the transient expression of specific
immunoregulatory genes within the equine lung for treatment
of inflammatory airway disease.
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